AB0774 Paradoxical reactions, especially psoriasis in rheumatology patients receiving biologic therapy from the Treasure database: a 5-year follow-up study
Authors: B. Yağiz, N. Lermi, B. N. Coşkun, E. Dalkiliç, S. Kiraz, A. İ. Ertenli, E. Bilgin, R. Yilmaz, A. Ateş, A. Tufan, R. Mercan, H. Cinakli, S. Akar, T. Kaşifoğlu, S. M. Türk, E. Gönüllü, A. Erden, C. Bes, H. Emmungil, U. Kalyoncu, Y. Pehlivan
Journal: Annals of the Rheumatic Diseases (2022)

Background Biologic agents have altered our ability to treat chronic inflammatory diseases effectively. Although paradoxical reactions (PRs) were initially described with TNF-α inhibitors, they have been reported with newly developed biologic agents or classes too (1). Due to the potential consequences of PRs, it is critical to identify and treat these drug class side effects as soon as possible. Objectives The aim of this study was to characterize PRs, especially psoriasis, in a large cohort of patients treated with biologic agents and to investigate their clinical implications. Methods TReasure database, which was launched in 2017, is a web-based prospective observational cohort comprised of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) from 17 centers located throughout Turkey. Characteristics of patients with PRs and clinicians’ treatment approaches and outcomes were evaluated using descriptive statistics. Results 3147 RA and 6071 SpA patients were evaluated. 139 (1.5%) patients (40 (28.8%) with RA and 99 (71.29%) with SpA) developed a PRs (Table 1). The rate of paradoxical psoriasis was 90.6% and 9.7% of the patients had a family history of psoriasis. Females constituted 64% of the patients. The mean age was 46±12 years and the disease duration were 146±92 months. Mean time interval between the PRs and diagnosis was 99,6±86 months, whereas median 12 (1-132) months between the PRs and the biological agent. Adalimumab (30.9 %), etanercept (20.1 %), and infliximab (18.7 %) were the three most frequently used agents during the PRs. However, 8.6% of the patients developed PRs with non-TNF agents. Only seven patients (5.1%) who had PRs discontinued the drug, while 28 patients (20.6%) continued to receive the agent that caused the PRs. Majority of patients were switched to other TNF-α inhibitors (48.5%) and non-TNF agents (25.7%). When we limited our analysis to paradoxical psoriasis patients, we observed complete remission in 43.5% of patients and progression in only six (4.7 %) of patients. (Figure 1). Table 1. Characteristics of RA and SpA patients who developed paradoxical reactions N Patients (N, %) Paradoxical reactions (PRs) 139 Psoriasis 126 (90.6%) Uveitis 6 (4.3%) Sarcoidosis 2 (1.4%) IBD 1 (0.7%) Other* 4 (4.3%) Primary disease 139 RA 40 (28.8%) SpA 99 (71.29%) Time interval between PRs-diagnosis of RA/SpA (months) 124 99,6±86 † 72 (3-420) †† Time interval between PRs-biological onset (months) 126 22±25 † 12 (1-132) †† BMI, kg/m 2 123 28±5 † 27,8 (17,3-49,7) †† Smokers (Current/ex) 131 61 (46.6%) / 10 (8.5%) Biological agents used during PRs 139 TNF-α inhibitor used** 127 (91.3%) Secukinumab 2 (1.4%) Abatacept 6 (4.3%) Rituximab 4 (2.9%) Biological agents used after PRs 101 Etanercept 31 (22.8%) Adalimumab 15 (11%) Secukinumab 12 (8.8%) Other*** 43 (57.5%) PRs: Paradoxical reactions IBD: Inflammatory bowel disease. *Drug-induced lupus:3 Vasculitis:1. ** Adalimumab: 43 (30.9%), Etanercept: 28 (20.1%), Infliximab: 26 (18.7%), Certolizumab: 20 (14.4%), Golimumab: 10 (7.2%). *** Certolizumab: 9 (6.6%), Tofacitinib: 9 (6.6%), Infliximab: 7 (5.1%), Tocilizumab: 5 (3.7%), Golimumab: 4 (2.9%), Ustekinumab: 4 (2.9%), Rituximab:3 (2.2%), Abatacept: 1 (0.7%), Anakinra: 1 (0.7%). † mean ± standard deviation. †† median (min-max) Conclusion Clinicians should be aware that PRs may develop with biologic agents other than TNF-α inhibitors. Additionally, it is important to keep in mind that the development time of PRs could be variable. The mechanism(s) behind PRs remain unknown, and there is no currently available diagnostic or therapeutic protocol (2). The decision whether to continue or discontinue biologic agents should be individualized. We found that the majority of patients can be managed without discontinuing biologic agents. Finally, we believe that the experience of our large cohort can help physicians in clinical practice where sufficient protocol is lacking. References [1]Lluís Puig. Curr Probl Dermatol. 2018; 53:49-63. [2]Michael J Murphy. J Am Acad Dermatol. S0190-9622(20)33154-6. Disclosure of Interests None declared